It has long been established that cells and tissue growing in microgravity behave differently than those on Earth. The ongoing challenge for the experimental study of cell behavior under these conditions has been simulating the environment of microgravity so that complete laboratory studies can be conducted on Earth. This provides the obvious advantages of cost-effectiveness and safety.
To address this issue, NASA developed the bioreactor in the 1980s. Essentially, the bioreactor is a cylindrical vessel equipped with a membrane for gas exchange and ports for media exchange and sampling. As the bioreactor turns, the cells continually fall through the medium yet never hit bottom. Under these conditions, the cells form clusters that sometimes grow and differentiate much as they would in the body. Unfortunately however, on Earth the clusters become too large to fall slowly. This requires the research to be continued in the true weightlessness of space.
It has been well established that a number of cell types grow in the bioreactor on Earth for extended periods in ways that resemble tissue-like behavior. For this reason, the bioreactor provides cell culture studies with a new tool for the study of 3-dimensional cell growth and differentiation.
Bioreactors have been used aboard the Mir space station to grow larger cultures than even terrestrial Bioreactors can support. Several cancer types, including breast and colon cancer cells, have been studied in this manner. Continued research using the NASA Bioreactor is planned aboard the international Space Station.
NASA-developed tissue engineering technology has greatly facilitated advancements in the design of three-dimensional cellular constructs that exhibit many tissue-like qualities. The NASA rotating wall vessel (RWV) is a low shear, optimized suspension culture which, like a clinostat, maintains growing cellular constructs in a state of free fall via randomization of the gravity vector. Multicellular constructs are cultured under spatially unrestricted conditions during constant rotation of the vessel about its horizontal axis, resulting in time-averaging of the g vector to near zero. Significant changes in gene expression, cellular physiology and morphology occurring during three-dimensional growth in the RWV have been attributed to a variety of factors particular to this culture paradigm, including significantly reduced shear stress, altered gravitational influence (sometimes referred to as modeled or simulated microgravity), adequate mass transfer of nutrients and waste removal, and the generation of three-dimensional architecture itself. Each of these parameters is readily addressed in cell culture studies performed in the environment of space, where three-dimensional development occurs under conditions of true microgravity, fluid shear is absent and mass transfer may be controlled. In ground based studies, however, it has been difficult to separate these parameters from one another in order to examine the influence of each on three-dimensional cellular growth and function.
Therefore, what is needed is an efficacious method of simulating a microgravity environment thus allowing long-term three-dimensional (3D) development during in vitro cell and tissue culture. Commercially available magnetic beads are either too small for use as microcarriers in cell culture (diameters on the order of <10 um which are not feasible for use as cell culture supports), and/or they lack appropriate surface matrix coating to facilitate cell adherence, a requisite factor to maintain cell-cell interactions for 3D construct development during in vitro culture. Typical uses for commercially available magnetic beads are for cell and protein separation technology.